The overall goal of this project is to define the mechanisms of suppression of antibody responses during chronic Trypanosoma cruzi infections. Using recent information generated in our laboratories, experiments will be performed to define the cellular and molecular basis for the observed deficiency in interleukin 2 (IL2) in infected mice. In vitro co-culture and in vivo cell transfer experiments will be used to achieve these goals. Emphasis will be placed on using responses to non-parasite antigens to determine the mechanisms of immunosuppression, although parasite-specific responses will also be examined. Based on recent observations that T. cruzi extracts can also suppress immune responses, we will define the conditions under which this occurs and characterize the parasite molecule(s) involved.